1. Field of the Invention
The present invention relates new steroid compounds as important intermediates for the synthesis of brassinosteroids as well as a process for preparing same. More particularly, the present invention relates to new 3.alpha.,5-cyclo-22,23-dihydroxy-5.alpha.-steroid compounds of the general formula: ##STR2## wherein X is a hydroxyl group and Y is a hydrogen atom, or X and Y, taken together, form an oxo group; each of the two R' radicals is independently a hydrogen atom, an acyl group, a silyl group, an alkoxycarbonyl group or a benzyl group, or the two R' radicals, taken together, form an alkylidene or a carbonyl group, the stereo-configuration at the 22- and 23-positions being either 22R and 23R or 22S and 23S; and R" and R"' are independently of each other a hydrogen atom or a lower alkyl group, as well as a process for preparing same.
2. Description of the Prior Art
Brassinolide is a steroidal compound with a plant-growth regulating activity isolated in 1979 from pollens of Brassica napus L. and structurally determined to be (2R,3S,22R,23R,24S)-2,3,22,23-tetrahydroxy-24-methyl-B-homo-7-oxa-5.alpha. -cholestan-6-one [Nature 281, 216-217 (1979)]. Brassinolide is considered to be the 6th plant hormone subsequent to ethylene, auxin, gibberellin, cytokinin and abscicic acid, and is still being studied for its distribution in plants and its specific functions thereto. Thus, a number of processes have been reported hitherto for the synthesis of brassinolide and its analogues (generally called brassinosteroids) as well as their intermediate products, including J. B. Siddall et al., J. Am. Chem. Soc., 102, 6580, (1980); N. Ikekawa et al., J. Chem. Soc. Chem. Comn., 1980, 962 and J. Chem. Soc. Perkin Trans. I, 1984, 139; H. Nozaki et al., J. Am. Chem. Soc., 105, 4491, (1983); T. C. McMorris et al., J. Org. Chem., 49, 2833, (1984); J. Tsuji et al., Tetrahedron Letters, 26, 69, (1985); A. Ficchi et al., J. Org. Chem., 49, 4297, (1984); N. B. Mandana et al., Steroids, 38, 2864, (1981); K. Mori et al., Tetrahedron, 38, 2099, (1982); A. Ficchi et al., J. Chem. Soc. Perkin Trans. I, 1983, 383; and K. Mori et al., Tetrahedron, 40, 1767, (1984). As the structure of brassinosteroids is complicate, the synthesis of brassinosteroids requires a sequence of chemical reactions and usually consists of more than ten steps. The majority of the reported synthetic processes for brassinosteroids, e.g. the former seven processes are now carried out through the route as shown in the following Scheme 1 (the process of Siddall et al.): ##STR3##
According to the Siddall et al. process shown in Scheme 1, a known 3-hydroxy-5.sup..DELTA. -compound of the formula XIII is first converted with p-toluenesulfonyl chloride in pyridine into the corresponding 3-tosyloxy-5.sup..DELTA. -compound of the formula XX wherein the hydroxyl group in 3-position is protected by the ester group, and the latter 3-protected compound is then reacted with BH.sub.3 in tetrahydrofuran and H.sub.2 O.sub.2 in an aqueous solution of sodium hydroxide to form the corresponding 3-tosyloxy-6.beta.-hydroxy compound of the formula XXI. Next, the compound of the formula XXI is oxidized with pyridinium hydrochloride-chromic anhydride in methylene chloride to form the corresponding 3-tosyloxy-6-oxo compound of the formula XXII which is then reacted with LiBr in dimethylformamide to form a 2.sup..DELTA. -6-oxo compound of the formula XV-a which is one of the important known intermediate for the synthesis of brassinolide and its analogues.
The starting 3-hydroxy-5.sup..DELTA. -compound of the formula XIII can be prepared via several steps from stigmasterol according to one of the known processes as mentioned above. On the other hand, synthesis of brassinolide from the compound of the formula XV-a is known from several reports, for example, Ikekawa et al., J. Chem. Soc. Perkin Trans. I, 1984, 139. According to the Ikekawa et al. process, the compound of the formula XV-a is reacted with osmium tetraoxide and N-methylmorpholine oxide in n-butanol, tetrahydrofuran and water to form the corresponding 2.alpha.,3.alpha.-dihydroxy compound which is then treated with an aqueous solution of acetic acid to split off the acetonide group bonded to 22- and 23-positions thereby producing castasterone (2.alpha.,3.alpha.,22.beta.,23.beta.-tetrahydroxy-6-one compound). For acylation of the hydroxyl groups, castasterone is reacted with acetic anhydride and DMAP in the presence of pyridine to form the corresponding 2.alpha.,3.alpha.,22.beta.,23.beta.-tetraacetoxy-6-one compound which is then converted to brassinolide by introducing 7-oxa group into the ring B.
The process of Siddall et al. comprised of 4 steps for preparing the compound of the formula XV-a from the compound of the formula XIII involves in the step for preparing the compound XXI from the compound of the formula XX the use of diborane which is expensive and cumbersome to handle. Thus, the process of Siddall et al. is not suitable as a synthetic process for brassinolide on an industrial scale.
Further, a number of processes are proposed for the synthesis of brassinolide from stigmasterol not via the route wherein the compound of the formula XV-a. Among the known references aforementioned, for example, the latter four references disclose the routes for the synthesis of brassinolide not via the compound of the formula XV-a. However, these known processes involve a number of steps and afford brassinolide in a very low yield. Up to the present, the process of Mori et al. comprised of 16 steps in all is regarded to be the best process and affords brassinolide in the maximum total yield as high as 3%. Thus, there is a necessity in the synthesis of brassinolide and its analogues to make further improvement in these known processes for reducing the number of the steps thereby increasing the total yield of brassinolide. For this purpose, it is necessary to find a new route for reducing the number of the steps over the whole or part of the process for synthesizing brassinolide from stigmasterol.
Starting from stigmasterol, a number of processes, including the process of Siddall et al., are known for the synthesis of the compound of the formula XIII which is an intermediate for the synthesis of brassinolide through a route wherein the compound of the formula XV-a is prepared. However, these known processes involve steps wherein the reaction is complicate or difficult and the yield of the product is poor, and are not satisfactory for a process to be carried out on an industrial scale.
For the synthesis of brassinosteroids in a more economical manner and in a smaller number of steps, there is a great demand in the field of this art for improving the steps hardly operable on an industrial scale in the prior art processes or developing a new route for synthesizing brassinosteroids which can be carried out economically and industrially.